Over 3 million African children are HIV-infected, but there is limited information on the development, health and social conditions of HIV-positive (HIV+) and HIV-negative (HIV-) children born to HIV-infected mothers. This study will assess the effects of HIV infection on child health and survival, in a cohort of 72 HIV+ and 228 HIV- but affected children born to HIV-infected mothers followed over 3. Children born during the study and their mothers/caretakers will be seen at birth, 4-6 weeks, 6 and 12 months, and annually thereafter. The specific aims are: To assess the effects of HIV infection in the child and/or the mother on:1) birth outcomes (birth weight, gestational age), 2) child health (morbidity), 3) growth and development (anthropometry), 4) neurodevelopmental disability (cognitive, motor, and behavioral disorders), and 5) mortality. The effects of antiretroviral therapy on each of these outcomes will also be assessed. Statistical methods will include Kaplan-Meier survival methods with log-rank tests for time to event analyses; proportional hazards models to estimate adjusted relative hazards for child outcomes with time-independent/dependent covariates; and regression methods for repeated measurements using population-average (marginal) and growth (conditional) models. The models will integrate the individual's baseline information, time-dependent risk factors, and recurrent event history into covariates for predicting future events, and provide a form of trajectory analyses. The study is nested within a decade-long community cohort in rural Rakai District, Uganda, which provides extensive information on maternal HIV status, sociodemographic, behavioral and health characteristics; and detailed data on households. The Rakai Program has an extensive field, clinical, laboratory and data management infrastructure. The multidisciplinary research team has the requisite expertise in epidemiology, clinical research, assessment of morbidity and disabilities, and in statistical analyses. In 2004, the Rakai Program received PEPFAR support for ARV provision and in 2005 was awarded a RO1 to assess ARV effects on HIV epidemiology and behaviors (1 R01 HD050180-01). However, the RO1 does not provide resources for detailed pediatric evaluations, particularly of neurodevelopmental disabilities, which will be a primary and original focus of this training and research application. Embedding the proposed study within the Rakai cohort draws upon unique resources and allows substantial cost savings. This study will provide critical information to guide interventions for improved care of HIV infected and HIV affected children in rural Uganda.